Chronic lymphocytic leukemia (CLL) is a hematological malignancy characterized by the clonal expansion of naive B-lymphocytes mainly in G0 phase of the cell cycle. CLL results in the accumulation of mature immunologically defective lymphocytes in the G0 phase. The disease is further characterized by the accumulation of B-lymphocytes in bone marrow, lymph nodes, spleen, and liver. In CLL patients, both the B and T cells are ineffective in their response to antigens and are associated with hypogammaglobulinemia and susceptibility to infectious diseases. The end stages of the disease results in the failure of production of myeloid and erythroid marrow elements as well as the presence of lymphoid masses. It is currently believed that the defective lymphocytes in CLL patients are produced at a normal rate as in healthy individuals, but fail to undergo appropriate apoptosis.
Currently, existing therapies and treatment protocols for advanced clinical stages have met with only partial success. Traditional drug treatments have involved combinations of chlorambucil (an alkylating agent) and prednisone (corticoid steroid). More recently, the purine analog fludarabine has been shown to have positive effects on new and pre-treated CLL patients. However, such drug treatments pose undesirable side effects for some patients. Further, some patients develop resistance to a particular drug.
The use of UVA radiation in an extracorporeal photo chemotherapy has been tested in CLL patients and has brought about improvements in T-cell lymphoma patients, but showed no clinical effect in CLL patients. (Wieselthier, J. S. et al Inefficacy of Extracorporeal Phytochemotherapy in the Treatment of T-cell Chronic Lymphocytic Leukemia: Preliminary Results. American Journal of Hematology, 41, 123-127 (1992) and (Edelson, R. L. “Photopheresis: A Clinically Relevant Immunobiologic Response Modifier” ANN NY Sciences, Vol. 636 p. 154-164 (1991)) and which are both incorporated herein by reference.
CML is a disorder associated with the Philadelphia translocation chromosomal aberration (long arms of chromosomes 9 and 22) and cytogenetic-molecular changes acquired during the clonal disease progression. CML is characterized by the expansion of myeloid progenitor cells at various stages of maturation. Further, the progenitor cells are released prematurely into the circulation system and thereafter accumulate in extramedullary sites such as the spleen. For numerous years, treatment protocols have included therapeutic treatments with bulsafan and hydroxyurea. Both treatments may reduce symptoms, but do not prevent progression of the disease to the blastic phase and resulting patient death. Stem cell transplantation has been successful for qualifying patients. Recently, the drug Gleevic™ has been used as an effective therapy for CML patients with good clinical results. However, drug resistance has been recently reported for some patients taking Gleevic™.
Accordingly, there remains room for variation and improvements with respect to therapies and treatments for leukemia.